The proposed research is focused on the development of a 1000 W, 250 GHz gyrotron amplifier for Magnetic Resonance research. Time domain DNP/NMR and EPR experiments have emerged as important techniques for elucidating the structure, function, and dynamic properties of biological systems. The full implementation of these techniques at high frequency has been limited by the lack of microwave power. This proposal requests funding to develop a high power gyrotron amplifier producing nanosecond to microsecond pulses for DNP/NMR and EPR applications at 9T. This renewal proposal builds on the success of our previous research program to design, fabricate and demonstrate a novel 100 W, 140 GHz gyroamplifier for application at 5T. The 140 GHz gyroamplifier has demonstrated a power level of 400 W and bandwidth of 1 GHz in two microsecond pulsed operation at 140 GHz. The amplifier is stable, with no output power detected unless an input drive signal is applied. The amplifier has met all of its major goals and will now be applied to Magnetic Resonance re- search. The proposed 250 GHz gyrotron amplifier research program also benefits from a highly successful program of research at MIT on high frequency gyrotron oscillators for DNP/NMR and EPR applications. The proposed new 250 GHz gyroamplifier will operate at 30 kV, 0.75 A in a magnetic field of 9T with over 60 dB of saturated gain. In order to optimize the performance of the Magnetic Resonance systems operating with high frequency microwaves (THz radiation), we also propose to develop optimized components such as transmission lines, nanosecond switches, and resonators. Progress in THz technology is also valuable for conventional spectroscopy of biological samples, cancer imaging and, possibly, cancer therapy. For NMR, signal intensities are intrinsically low due to the small gyromagnetic ratios of the observed nuclei. It is therefore crucial to develop methods to enhance the sensitivity of NMR experiments. DNP spectroscopy has been developed to routinely record 1D and 2D DNP enhanced magic angle spinning (MAS) spectra of membrane and soluble proteins using biradicals as polarizing agents. The availability of intense microwave pulses will allow the development of new polarization transfer schemes based on coherent processes, such as electron-nuclear Hartmann-Hahn cross polarization schemes, which are more favorable at high magnetic fields. For EPR, the increased excitation bandwidth of the intense microwave pulses of the proposed gyroamplifier will provide us with the possibility to perform high-field Fourier transform spectroscopy and DQ EPR experiments to determine the distance and the orientation between two electron spins in systems of biological interest. Funding of this continuation proposal is crucial to maintaining progress in this important field of spectroscopic research on biomolecules. PUBLIC HEALTH RELEVANCE: The proposed research is directed at building a high frequency microwave source that will greatly enhance the sensitivity of Nuclear Magnetic Resonance (NMR) and Electron Paramagnetic Resonance (EPR) spectrometers and will therefore help to elucidate the properties of biomolecules. The improved techniques will lead to increased understanding of the structure of amyloid and membrane proteins which are key to understanding their role in biological systems. High frequency microwaves can also be used in imaging tissue, in detecting cancer and, possibly, in cancer therapy.